PMID- 23796784
OWN - NLM
STAT- MEDLINE
DCOM- 20131216
LR  - 20220310
IS  - 1530-6860 (Electronic)
IS  - 0892-6638 (Linking)
VI  - 27
IP  - 10
DP  - 2013 Oct
TI  - alpha1,6-Fucosylation regulates neurite formation via the activin/phospho-Smad2 
      pathway in PC12 cells: the implicated dual effects of Fut8 for 
      TGF-beta/activin-mediated signaling.
PG  - 3947-58
LID - 10.1096/fj.12-225805 [doi]
AB  - It is well known that alpha1,6-fucosyltransferase (Fut8) and its products, 
      alpha1,6-fucosylated N-glycans, are highly expressed in brain tissue. Recently, we 
      reported that Fut8-knockout mice exhibited multiple behavioral abnormalities with 
      a schizophrenia-like phenotype, suggesting that alpha1,6-fucosylation plays important 
      roles in the brain and neuron system. In the present study, we screened several 
      neural cell lines and found that PC12 cells express the highest levels of 
      alpha1,6-fucosylation. The knockdown (KD) of Fut8 promoted a significant enhancement 
      of neurite formation and induction of neurofilament expression. Surprisingly, the 
      levels of phospho-Smad2 were greatly increased in the KD cells. Finally, we found 
      that the activin-mediated signal pathway was essential for these changes in KD 
      cells. Exogenous activin, not TGF-beta1, induced neurite outgrowth and 
      phospho-Smad2. In addition, the alpha1,6-fucosylation level on the activin receptors 
      was greatly decreased in KD cells, while the total expression level was 
      unchanged, suggesting that alpha1,6-fucosylation negatively regulated 
      activin-mediated signaling. Furthermore, inhibition of activin receptor-mediated 
      signaling or restoration of Fut8 expression rescued cell morphology and 
      phospho-Smad2 levels, which were enhanced in KD cells. Considering the fact that 
      alpha1,6-fucosylation is important for TGF-beta-mediated signaling, the results of this 
      study strongly suggest that Fut8 plays a dual role in TGF-beta/activin-mediated 
      signaling.
FAU - Gu, Wei
AU  - Gu W
AD  - 1Division of Regulatory Glycobiology, Institute of Molecular Biomembrane and 
      Glycobiology, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, 
      Sendai Miyagi, 981-8558, Japan. jgu@tohoku-pharm.ac.jp.
FAU - Fukuda, Tomohiko
AU  - Fukuda T
FAU - Isaji, Tomoya
AU  - Isaji T
FAU - Hashimoto, Hirokazu
AU  - Hashimoto H
FAU - Wang, Yuqin
AU  - Wang Y
FAU - Gu, Jianguo
AU  - Gu J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130624
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - 0 (Smad2 Protein)
RN  - 0 (Smad2 protein, rat)
RN  - 0 (Transforming Growth Factor beta)
RN  - 104625-48-1 (Activins)
RN  - EC 2.4.1.- (Fucosyltransferases)
RN  - EC 2.4.1.68 (Glycoprotein 6-alpha-L-fucosyltransferase)
SB  - IM
MH  - Activins/*metabolism
MH  - Animals
MH  - Fucosyltransferases/genetics/*metabolism
MH  - Gene Expression Regulation/physiology
MH  - Gene Knockdown Techniques
MH  - Mice
MH  - Neurites/*metabolism
MH  - PC12 Cells
MH  - Rats
MH  - Signal Transduction/*physiology
MH  - Smad2 Protein/*metabolism
MH  - Transforming Growth Factor beta/genetics/*metabolism
OTO - NOTNLM
OT  - N-glycosylation
OT  - cell differentiation
OT  - glycosyltransferase
EDAT- 2013/06/26 06:00
MHDA- 2013/12/18 06:00
CRDT- 2013/06/26 06:00
PHST- 2013/06/26 06:00 [entrez]
PHST- 2013/06/26 06:00 [pubmed]
PHST- 2013/12/18 06:00 [medline]
AID - fj.12-225805 [pii]
AID - 10.1096/fj.12-225805 [doi]
PST - ppublish
SO  - FASEB J. 2013 Oct;27(10):3947-58. doi: 10.1096/fj.12-225805. Epub 2013 Jun 24.